Project Summary Impairments in social communicative behaviors are primary in autism. Two of the most affected behaviors include visual attention to faces and the ability to understand how eye gaze provides important information about the actions and intentions of others. One theory is that the neural systems for face processing are fundamentally compromised. However, our recent brain imaging findings suggest that there are contexts in which these neural systems respond normally to animal faces, indicating that they are not compromised, but likely tuned differently in autism. As a result, we hypothesize that there is an early disruption in the learning environment that leads to this altered pattern of tuning and that this disruption is reflected by reduced attention to faces and more attention to non-social stimuli. The long-term consequence is that individuals with autism may never have learned about the functional significance of social signals from the face, like eye gaze cues. We hypothesize that it may be possible to re-tune the face processing system and social looking behaviors in autism by employing effective methods for encouraging individuals to focus visual attention on faces and discover the functional significance of eye gaze cues. In turn, this may begin to treat symptoms of autism and improve social functioning. We propose to develop and test an intervention for adolescents with autism that employs evidence-based ?serious game? principles (e.g., storylines, long-term goals, scaling difficulty). ?Serious games? are unique intervention tools that foster learning of difficult skills, with the goal of improving real-world outcomes. Our intervention game is designed to scaffold learning to focus attention on faces while interpreting eye gaze cues from animated human characters in the context of a narrative storyline. Participants have to discover that eye gaze cues are useful for guiding their own goal-directed behavior to solve problems in the game. This simulates the way social information cues are discovered and used in the real world and, therefore, is more likely to generalize to real-world behavior. We propose a two-stage exploratory study to test this intervention. In the R61 phase, we will utilize behavioral and eye-tracking methods to examine pre- to post-test changes on our target mechanisms (attention to faces and sensitivity to eye gaze cues) in adolescents who play the intervention game. In the R33 phase, we will conduct a small-scale RCT comparing the intervention game to an active control game to assess outcomes at multiple time points (pre-, post-, 6-month follow-up), and to evaluate improvements in a wide range of behaviors, from controlled lab-based tasks to uncontrolled, real-world social interactions. Our aims are evaluating 1) changes in the target mechanisms, 2) improved face-processing behaviors and real-world social communication behaviors, and 3) the relation between engagement of the target mechanisms and symptom outcomes. These goals represent significant innovation in the design of RCTs for computer-based interventions for autism, and hold tremendous promise for widespread and inexpensive dissemination.